Mercury compounds having therapeutic properties



' Patented Mar. 12,1929. i

Um'rsn srar-Es v Parent orrics.

AUGUST ALBEBHJ, OF MUNICH, AND JOHANN'ES PFLEGER, OF FRANKFORT OI\T THE- MAIN, GERMANY, ASSIGNORS, BY MESNE ASSIGNMENTS, T WINTHROP CHEMICAL ooMBANY, on NEW ORK; n. Y., A CORPORATION or NEW YORK.

. I ME CURY comrounnsnAvIuGaHE APEUTic rnornamrns.

, No Ih'awing.. Application filed liovember 24, 1923, Serial No. 676,845, and in Germany December 5, 1922.

This application is aco ntinuation in part of applicants copending application S. N. .671,-

076, filed Oct. 27, 1923.

5v mercury compounds show valuable therapeutical properties, the most variated types-of classes of organic bodies were mercurated and their behaviour towards the animal organisms tested, the aim. in'view being to find new and usefulweapons for fighting-diseases.

Theresults of these investigations were very poor indeed. 'Only a very small number I I of organic compounds could be introduced as medicines into-practical use. I ,We have now succeeded in finding a new class of organic mercury compounds, several represeritativesof which show' an extremely strong therapeutical effect. The chief characteristic of the new compopunds is the presi .ence in the molecule of the very active group 1 C 0 or C :N, the latter of which may be de-' rived from the formerl, f

p The following are some compounds repre: *SBIltillg the various classes of the above mentioned types: hydro-oxyacetophenone, aminoacetophenone, halogen-acetophenone', aceto phenoncarboxylic acid, acetophenonsulphonic acid, acetophenonarrson'ic acid, acetophenonecarbotylic acid-semicarbazone, acetophenonarsonic acid-semicarbazon etc. The composition' of the compounds in question may beexpressed by the following formulae:

in which R means an aromatic, R, an aliphatic radical. o

The mercurating of these (compounds is 40 carried out in various ways such. a by heating is mercurated directly or Working the mercury enters into the nucleus of thearomatic radical R or into the aliphatic k side chain R After it was recognized that several organic 'I he production of the mercury compounds derived from and corresponding to the following formulae a I AJ=NX and i may be carriedout in acordance with the above mentioned modifications. i (1) Either asubstance of the formula] R Y t=NX t.

(2) A substance of the formula is mercurat-ed and then brought into reaction in the well known manner with a body H NX. whereby generally, 4 the following reaction takes place: I

To show the way in which the invention may be carried out, we give the following examples: j

(1) 20 g. p-acetophenone carboxylic acid are mixed with 30 g. acetate of mercury. The mixture is kept in a preheated oil bath at about 130140 C. until the precipitation of the mercury oxide by caustic soda solution ceases. This takes as a rule from 15 to 25 minutes. The'inew compound is soluble in sodiumcarbonate and caustic alkali.

With the quantities as indicated above the acid is kept in excess. Thereby the formation of a dl-lnercury compound is avoided.

(2) If the molecule of the acid is treated with 2 mol. of mercury acetate, but otherwise treated in the same way as described in Exam- I ple (1) a dimercury compound is'formed, the

' (4) 0,8 g. p-chloric acetophenone constitution of which is probably ooonn o 0,5'g. p-acetophen one .arso nic acid are" 'cohol and the colourless residue drawn 0aand dried. The melting point is higher than 270 C. The structural formula of the prod: not formed in accordance with this example is as follows g.OOC.CH:

(5) 0,7 g. p-'hydroxy-acetophenone and 1,6 g. mercury acetate are Wellmixed and heated a short time at a temperature of more than 100 C. There'results a brown-resinous melt which is dissolved in acetic acid and which after addition of caustic solution gives a colourless precipitation. It dissolves easily in caustic solution in consequence .oflits content of hydroxyl. It decomposes at about 175 C. The structural formula of the product formed in accordance with this exam- I ple is as follows BOO-GOSH: I H Z v inaooc'cm I 6) If0,4 g. p-aminoacetophenone and 1g. mercury acetate are heated atQtempratures of more than 100 -.C., a dark brown melt --'N.NH.CO.'NH:

a meltingpoint.

results. After cooling it may be treated the following manner: The melt is dissolved in acetic acid, the solution filtered through animal charcoal and precipitates theyellow base With'caustic solution. It decomposes at about 215 C.

(7) 0,2 g. acetophenone well mixed with 0,3 g.. mercury acetate and heated for a short time at a temperature-be- Q ginning with C. The melt is stirred with Water," drawn ofi, separated and recrystallized with caustic solution.. The product is pre- 1 cipitated as a colourless powder out of the alkaline solution by making itacid. .The structural formula of the product formed in accordance with this examplejis as 1501-" "no coon, p f fi 'oooomi OOH ' '8 2 5' -acetophenonearsonic acid are lows dissolved in 5 mol. n-sodium hydroxide. i Tothe solution are added 2.2 g. of precipitated mercuric oxide. Atordinary temperature the reaction takes place and the whole of the salycilic acid are mercuric oxide goes into solution. The'clear' solution after being filtered is slightly acidified and the crystalline precipitate, of the arsonic acid is separated by suction.

accordance withthi s'example is as follows H g.0H g .(9) 3 g. p-acetophenonearsonic acid semicarbazone are' dissolved in 'n-sodium hydroxide solution. To the solution are added 2 g. of precipitated mercuric. oxide. The reaction takes place even at ordinary temperature; the mercuric oxide going into solution; the solution is drawn oil, the clear filtrate is neutralizedand the formed mercury compound drawn oif and dried. Theiacid may be converted into readily soluble salt- The "structuralformula of the product formed in by neutralizing it with alkali. This can be separated from the aqueoussolution in solid" form for instance by precipitation with alcohol. The following equation containsthe a structural'formulae above reaction.

showing the course of the i omH oH' =N.Nn.oo.Nm

' What we claim is:

1. A new mercu ry compound having therapeutic properties comprising a compound of the general formula I p I =NX, mercurated, R1 i in which X represents either a hydrogen R I JI =N X, mercurated,

wherein X represents'the radical NH CO fjNH R an aromatic and 'R -hydrogem or an aliphatic radical; and wherein the nitrogen is connected with the carbon atom ina non-cyclic" combination;

3. A new mercury compound having therapeutic properties comprising a compound of the general formula R & ==N- NHCO-NHz, mercurated,

wherein R- represents an aromatic radical.

4. A new mercury compound havlng therapeutic properties comprising a compound In testimony 'vhereof we have signed our names to this specification.

AUGUST ALBERT. JOH. PFLEGER. 

